Our long range aim is to understand the special functions of cytoplasmic genetic systems in the control of normal growth and development at the cell and molecular levels. Of particular interest is the possible role of cytoplasmic genes in the etiology of cancer and other pathological genetically determined disorders. We have developed a unique method for genetic analysis by mutagenesis, recombination, and mapping of cytoplasmic genes, identified by their non-Mendelian pattern of inheritance. We are attempting to "saturate the map" to estimate the genomic size from genetic data and compare it with estimates from physical studies. A further aim is the search for additional cytoplasmic linkage groups, as well as the identification of each with a specific cytoplasmic organelle or structure. Mitochondrial mutants are of especial interest because of their universal presence and importance in all eukaryotic cells. We are examining the functions of cytoplasmic genes by biochemical studies of cytoplasmic mutant strains. In particular we are looking for ribosomal and membrane proteins altered by mutation of cytoplasmic genes. We are continuing previous studies of chloroplast DNA to find ways of fractionating, in order to study the redundancy we found by the use of reannealing kinetic techniques.